Superfund Research Program
Development and Application of Biomarkers of Exposure
Project Leader: Stephen M. Rappaport (University of California-Berkeley)
Grant Number: P42ES005948
Funding Period: 1995 - 2011
Project investigators continue to make progress in the use of biomarkers to understand the complex human metabolism of benzene and other ubiquitous environmental carcinogens, notably naphthalene. A host of biomarkers is being applied in studies of benzene- and naphthalene-exposed populations, including protein adducts of several reactive metabolites of benzene and naphthalene, of benzene and naphthalene in breath and urine, and of benzene and naphthalene metabolites in urine. Using these biomarkers, they are evaluating the uptake and metabolism of benzene and naphthalene over a wide range of human exposures. Human biomarkers are measured in samples of blood, urine, and breath obtained in prior studies and by collaborators at other institutions. Benzene metabolites of interest include reactive intermediates, i.e., benzene oxide and 1,2- and 1,4-benzoquinone, as well as the following stable urinary products: phenol, catechol, hydroquinone, trihydroxybenzene, E,E-muconic acid and S-phenylmercapturic acid. The analogous naphthalene metabolites are naphthalene oxide, the naphthoquinones, and urinary naphthols. Project investigators have now developed assays for these biomarkers and have measured them in well over 1000 subjects exposed to benzene and/or naphthalene in a host of industrial populations (automobile mechanics, jet-fuel workers, shoe manufacturing workers, workers in industries using benzene as a solvent, coke-oven workers) as well as control populations. They are currently analyzing these data to explore the relationships between biomarkers and exposure to benzene and naphthalene and to determine effects of physiological and genetic factors on levels of biomarkers.